Akari Therapeutics, Plc (Nasdaq: AKTX), a biopharmaceutical company
focused on innovative therapeutics to treat autoimmune and
inflammatory diseases where the complement and/or leukotriene
systems are implicated, announces new preclinical data indicating
that nomacopan significantly reduced both retinal inflammation and
intraocular VEGF.
Treatment of back-of-the-eye diseases, including angiogenic
ocular diseases with new blood vessel growth such as diabetic
retinopathy and wet age-related macular degeneration (AMD), is a
multi-billion dollar market. VEGF promotes angiogenesis in these
latter conditions, and inhibition of VEGF with antibodies such as
Lucentis® and antagonists such as Macugen® and Eyelea® form the
mainstay of treatment of wet AMD. In contrast, complement
inhibitors are being explored as a treatment for dry AMD.
“Despite the successful use of VEGF inhibitors, many patients
with AMD and other back-of-the-eye diseases remain sub-optimally
treated,” said Professor Virginia Calder, University College of
London (UCL), Institute of Ophthalmology. “This reflects the
complex natural history and pathology of these retinal diseases. An
agent such as nomacopan that appears to combine anti-inflammatory
activity with VEGF and complement inhibition has the potential to
improve treatment options, highlighting the importance of these
pathways and the degree to which their dysregulation is implicated
in different sight-threatening conditions.”
Professor Calder and colleagues at UCL have undertaken new work
comparing the therapeutic efficacy of nomacopan, PAS-nomacopan, and
a monoclonal anti-VEGF antibody all administered intravitreally.
Their work utilized an established 26-day model of severe
experimental autoimmune uveitis (EAU) in mice which results in
elevated VEGF and retinal inflammation mediated by influx of
lymphocytes which thereby mimics the pathology seen in several
back-of the eye diseases. Drug treatments were administered on day
15 once disease was established and ongoing.
PAS-nomacopan was found to reduce intraocular VEGF levels by as
much as the anti-VEGF antibody with 74% (p=0.04) and 68% (p=0.05)
reductions respectively, compared to saline control. Furthermore,
while clinically assessed inflammation increased in both the
control and anti-VEGF groups by 49% and 33%, respectively,
PAS-nomacopan treatment showed a 9% reduction in inflammation
assessed by retinal fundoscopy (p=0.02), supporting nomacopan’s
therapeutic activity across multiple pathogenic pathways.
PAS-nomacopan, which has a very large functional molecular
weight of 670kDa, due to use of the PASylationTM technology (Kuhn
et al. 20161), was more effective than nomacopan (17kDa) in
reducing both VEGF levels and inflammation, probably reflecting
longer residency time of PAS-nomacopan in the eye.
The rationale for using nomacopan as a treatment for the
back-of-the-eye was initiated by the discovery that cell-activating
receptors (C5aR1 and BLT1) that bind to complement C5a and LTB4 are
expressed by retinal inflammatory cells in the back of the eye.
Nomacopan inhibits C5 activation preventing formation of C5a and
captures LTB4, and thereby has the potential to inhibit C5a and
LTB4 signalling via the receptors identified in the retina.
Furthermore, as previously reported in an EAU model (April 26,
2019), nomacopan significantly reduced inflammatory markers such as
the cytokine IL-17 together with clinical and histological
inflammation. Nomacopan’s activity appeared to be equivalent to
potent corticosteroids, the standard of care treatment for acute
posterior non-infective uveitis.
These results suggest the potential for nomacopan as a
first-line treatment for multiple back-of-the-eye diseases in that
the single drug has now been demonstrated to mitigate three
pathways implicated in uveal, macular and retinal diseases:
|
• |
Inhibition of VEGF release, a key driver of wet AMD |
|
• |
Reduced expression of inflammatory mediators such as the cytokine
IL-17 |
|
• |
Inhibition of the complement pathway, implicated in dry AMD |
Wynne Weston-Davies, Medical Director, Akari Therapeutics, said,
“We have an ongoing Phase II trial in atopic keratoconjunctivitis
(a surface of the eye disease) with nomacopan and are pleased to
report new encouraging pre-clinical data in the back of the eye
with the differentiated long-acting PAS-nomacopan. We are now
actively exploring other pre-clinical models in diseases such as
AMD and how best to develop these findings in the clinic where
there remains a significant unmet need.”
1Nomacopan, formerly Coversin, accepted as International
Non-proprietary Name by World Health Organization.
About Akari Therapeutics
Akari is a biopharmaceutical company focused on developing
inhibitors of acute and chronic inflammation, specifically for the
treatment of rare and orphan diseases, in particular those where
the complement (C5) or leukotriene (LTB4) systems, or both
complement and leukotrienes together, play a primary role in
disease progression. Akari's lead drug candidate, nomacopan
(formerly known as Coversin), is a C5 complement inhibitor that
also independently and specifically inhibits leukotriene B4 (LTB4).
Nomacopan is currently being clinically evaluated in four
indications: bullous pemphigoid (BP), atopic keratoconjunctivitis
(AKC), thrombotic microangiopathy (TMA), and paroxysmal nocturnal
hemoglobinuria (PNH). Akari believes that the dual action of
nomacopan on both C5 and LTB4 may be beneficial in AKC and BP.
Akari is also developing other tick derived proteins, including
longer acting versions.
Cautionary Note Regarding Forward-Looking
Statements
Certain statements in this press release constitute
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995 regarding, among other
things, statements related to the offering, the expected gross
proceeds and the expected closing of the offering. These
forward-looking statements reflect our current views about our
plans, intentions, expectations, strategies and prospects, which
are based on the information currently available to us and on
assumptions we have made. Although we believe that our plans,
intentions, expectations, strategies and prospects as reflected in
or suggested by those forward-looking statements are reasonable, we
can give no assurance that the plans, intentions, expectations or
strategies will be attained or achieved. Furthermore, actual
results may differ materially from those described in the
forward-looking statements and will be affected by a variety of
risks and factors that are beyond our control. Such risks and
uncertainties for our company include, but are not limited to:
needs for additional capital to fund our operations, our ability to
continue as a going concern; uncertainties of cash flows and
inability to meet working capital needs; an inability or delay in
obtaining required regulatory approvals for nomacopan and any other
product candidates, which may result in unexpected cost
expenditures; our ability to obtain orphan drug designation in
additional indications; risks inherent in drug development in
general; uncertainties in obtaining successful clinical results for
nomacopan and any other product candidates and unexpected costs
that may result therefrom; our ability to enter into collaborative,
licensing, and other commercial relationships and on terms
commercially reasonable to us; difficulties enrolling
patients in our clinical trials; failure to realize any value of
nomacopan and any other product candidates developed and being
developed in light of inherent risks and difficulties involved in
successfully bringing product candidates to market; inability to
develop new product candidates and support existing product
candidates; the approval by the FDA and EMA and any other similar
foreign regulatory authorities of other competing or superior
products brought to market; risks resulting from unforeseen side
effects; risk that the market for nomacopan may not be as large as
expected; risks associated with the departure of our former Chief
Executive Officers and other executive officers; risks associated
with the SEC investigation; inability to obtain, maintain and
enforce patents and other intellectual property rights or the
unexpected costs associated with such enforcement or litigation;
inability to obtain and maintain commercial manufacturing
arrangements with third party manufacturers or establish commercial
scale manufacturing capabilities; the inability to timely source
adequate supply of our active pharmaceutical ingredients from third
party manufacturers on whom the company depends; unexpected cost
increases and pricing pressures and risks and other risk factors
detailed in our public filings with the U.S. Securities and
Exchange Commission, including our most recently filed Annual
Report on Form 20-F filed with the SEC. Except as otherwise noted,
these forward-looking statements speak only as of the date of this
press release and we undertake no obligation to update or revise
any of these statements to reflect events or circumstances
occurring after this press release. We caution investors not to
place considerable reliance on the forward-looking statements
contained in this press release.
For more information
Investor Contact:
Peter VozzoWestwicke(443) 213-0505peter.vozzo@westwicke.com
Media Contact:
Sukaina Virji / Nicholas Brown / Lizzie SeeleyConsilium
Strategic Communications+44 (0)20 3709
5700Akari@consilium-comms.com
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